The objectives of this proposal are to purify and characterize gallbladder mucin glycoproteins from experimental animals and humans; to determine the effect of mucin gel on nucleation of cholesterol gallstones; and to study factors such as gut hormones, adrenergic and cholinergic agonists, and prostaglandins on ballbladder mucus release. The significance of this study relates to the role of gallbladder mucin in the pathophysiology of cholesterol gallstones. Work in our laboratory indicates that cholesterol feeding in prairie dogs causes marked mucin hypersecretion before the appearance of cholesterol gallstones. Inhibition of mucin secretion with aspirin prevented stone formation in cholesterol-fed animals. Mucin gel was shown to nucleate cholesterol from supersaturted bile in vitro. Based on these results, we plan to apply standard biochemical separation procedures to purify mucin, avoiding harsh conditions. We will study the interaction of mucin and biliary lipids by polarizing light microscopy. The factors that regulate the secretion of mucin from the gallbladder will be studied in organ culture. The effect of inhibitors of mucin secretion on gallstone formation will be studied systematically in prairie dogs fed cholesterol. These studies will provide a better understanding of the contribution of mucin to gallstone disease and may provide a therapeutic approach to the prevention of gallstones in high risk patients. This study will also provide basic information regarding the biochemistry and physiology of gallbladder mucin.